Siavash Shariatzadeh

All Publications

• Distraction Enterogenesis Induces Desert Hedgehog in the Lengthened Murine Colon. Journal of pediatric surgery Shariatzadeh, S., Sazi, A. T., Dunn, J. C. 2024: 161960

  Abstract

  Distraction enterogenesis lengthens the intestine through applied mechanical stress. The Hedgehog pathway (Hh) is responsible for intestinal tract development and directing the multi-layer patterning of the intestinal lumen. This study investigates the alteration in the principal components of this pathway in spring-mediated colonic lengthening.Samples from the murine cecal lengthening model were used to study Hh alteration during the cecal lengthening process. Primary components of this pathway were analyzed using RT-qPCR and immunostaining after 7 and 14 days of force application. The spring-mediated lengthened segments were compared to untreated control segments within each animal.The spring-treated segments showed a 50% increase in length. There was a significant increase in the expression of the Desert Hedgehog ligand as opposed to the Sonic Hedgehog and Indian Hedgehog ligands. Additionally, the downstream targets of the pathway, Gli1, Gli2, and Gli3, were significantly overexpressed. The highest alterations in these components occurred at the earlier time point, after 7 days.These findings highlight the contribution of the conserved Hedgehog developmental pathway during mechanical force-induced cecal lengthening, primarily through the Desert Hedgehog ligand. These data suggest that the Desert Hedgehog pathway may serve as therapeutic targets for intestinal regeneration.

  View details for DOI 10.1016/j.jpedsurg.2024.161960

  View details for PubMedID 39349347

• Single-cell transcriptional analysis of irradiated skin reveals changes in fibroblast subpopulations and variability in caveolin expression. Radiation oncology (London, England) Kameni, L. E., Griffin, M., Berry, C. E., Shariatzadeh, S., Downer, M. A., Valencia, C., Fazilat, A. Z., Nazerali, R., Momeni, A., Januszyk, M., Longaker, M. T., Wan, D. C. 2024; 19 (1): 82

  Abstract

  Radiation-induced fibrosis (RIF) is an important late complication of radiation therapy, and the resulting damaging effects of RIF can significantly impact reconstructive outcomes. There is currently a paucity of effective treatment options available, likely due to the continuing knowledge gap surrounding the cellular mechanisms involved. In this study, detailed analyses of irradiated and non-irradiated human skin samples were performed incorporating histological and single-cell transcriptional analysis to identify novel features guiding development of skin fibrosis following radiation injury.Paired irradiated and contralateral non-irradiated skin samples were obtained from six female patients undergoing post-oncologic breast reconstruction. Skin samples underwent histological evaluation, immunohistochemistry, and biomechanical testing. Single-cell RNA sequencing was performed using the 10X single cell platform. Cells were separated into clusters using Seurat in R. The SingleR classifier was applied to ascribe cell type identities to each cluster. Differentially expressed genes characteristic to each cluster were then determined using non-parametric testing.Comparing irradiated and non-irradiated skin, epidermal atrophy, dermal thickening, and evidence of thick, disorganized collagen deposition within the extracellular matrix of irradiated skin were readily appreciated on histology. These histologic features were associated with stiffness that was higher in irradiated skin. Single-cell RNA sequencing revealed six predominant cell types. Focusing on fibroblasts/stromal lineage cells, five distinct transcriptional clusters (Clusters 0-4) were identified. Interestingly, while all clusters were noted to express Cav1, Cluster 2 was the only one to also express Cav2. Immunohistochemistry demonstrated increased expression of Cav2 in irradiated skin, whereas Cav1 was more readily identified in non-irradiated skin, suggesting Cav1 and Cav2 may act antagonistically to modulate fibrotic cellular responses.In response to radiation therapy, specific changes to fibroblast subpopulations and enhanced Cav2 expression may contribute to fibrosis. Altogether, this study introduces a novel pathway of caveolin involvement which may contribute to fibrotic development following radiation injury.

  View details for DOI 10.1186/s13014-024-02472-z

  View details for PubMedID 38926892

  View details for PubMedCentralID 6329848

• Mechanosensitivity and Adaptive Capacity of the Intestinal Wall in a Partial Obstruction Murine Model Shariatzadeh, S., Thomas, A. A., Lopez, N. D., Martin, M. G., Dunn, J. C. LIPPINCOTT WILLIAMS & WILKINS. 2023: S356

  View details for Web of Science ID 001094086301171

• Non-Canonical Ciliary-Mediated Hedgehog Signaling Underlying Cecal Lengthening Shariatzadeh, S., Thomas, A. A., Portelli, K., Wood, L., Park, J., Dunn, J. C. LIPPINCOTT WILLIAMS & WILKINS. 2023: S373

  View details for Web of Science ID 001094086301210